Table 2.
Studies targeting CD40 in therapeutic treatments of kidney disease.
| Approach | Distribution | Kidney Disease Model | Prevention Effects | Drawbacks |
|---|---|---|---|---|
| CD40L antagonist (MR1) | Non-specific | Renal ischemia reperfusion (IRI) in mouse | MR1 in combination with MyD88 inhibitor restored survival rate, decreased serum creatinine (Cr), blood urea nitrogen (BUN), attenuated tubular damage and apoptosis, and reduced inflammatory cytokines in the kidney [116] | Risk of thromboembolism events by CD40L antibody |
| DNA vaccination | Dendritic cells | Heymann nephritis (HN) in rats | Block B-cell activation and CD8+ T-cells proliferation, reduced proteinuria, glomerulosclerosis, tubular atrophy, immune cell infiltration and IgG deposition [120] | Targeting dendritic cells, limited to autoimmune-mediated kidney disease |
| Autoimmune glomerulonephritis in rats | Attenuated glomerulosclerosis and tubular atrophy; reduced immune cell infiltration [121] | |||
| siRNA | Non-specific | Unilateral ureteral obstruction (UUO) in mouse | Attenuated tubular dilation and interstitial fibrosis, reduced macrophage and CD3+ T-cells infiltration, and reduced gene expression of pro-fibrotic cytokines [123] | Lack of ability to target distribution, triggers immune responses and has off-target side effects |
| Renal ischemia reperfusion (IRI) in rats | Attenuated renal injury, CD68+ macrophages and CD3+ T-cells infiltration, pro-inflammatory genes expression, and suppressed overexpression of genes related to cell cycle [124] | |||
| Lupus nephritis in mouse | Cholesterol-conjugated anti-CD40-siRNA attenuated proteinuria, extra-capillary proliferation, interstitial infiltrates, tubular atrophy, and interstitial fibrosis; reduced serum anti-dsDNA antibodies and circulating pro-inflammatory cytokines [125] | |||
| Generation 2.5 antisense oligonucleotide (ASO) | Favorable distribution into organs including kidney | Doxorubicin (DOX)-induced nephropathy and UUO model in mouse | Improved glomerular nephropathy, interstitial and mesangial expansion, granular tubular casts, and reduced renal injury markers [91] | Potential for nephrotoxicity and hepatotoxicity |